Maternal obesity predisposes offspring to metabolic dysfunction and Non-Alcoholic Fatty Liver Disease (NAFLD). Melanocortin-4 receptor (Mc4r)-deficient mouse models exhibit obesity during adulthood. Here, we aim to determine the influence of the Mc4r gene on the liver of mice subjected to perinatal diet-induced obesity. Female mice heterozygous for Mc4r fed an obesogenic or a control diet for 5 weeks were mated with heterozygous males, with the same diet continued throughout pregnancy and lactation, generating four offspring groups: control wild type (C_wt), control knockout (C_KO), obese wild type (Ob_wt), and obese knockout (Ob_KO). At 21 days, offspring were genotyped, weaned onto a control diet, and sacrificed at 6 months old. Offspring phenotypic characteristics, plasma biochemical profile, liver histology, and hepatic gene expression were analyzed. Mc4r_ko offspring showed higher body, liver and adipose tissue weights respect to the wild type animals. Histological examination showed mild hepatic steatosis in offspring group C_KO. The expression of hepatic genes involved in regulating inflammation, fibrosis, and immune cell infiltration were upregulated by the absence of the Mc4r gene. These results demonstrate that maternal obesogenic feeding during the perinatal period programs offspring obesity development with involvement of the Mc4r system.

• MeSH
• alanintransaminasa krev   MeSH
• aspartátaminotransferasy krev   MeSH
• fyziologie výživy v mateřství * MeSH
• játra metabolismus   MeSH
• krevní glukóza metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši obézní MeSH
• myši MeSH
• obezita genetika   MeSH
• perinatální péče MeSH
• receptor melanokortinový typ 4 nedostatek   genetika   MeSH
• regulace genové exprese MeSH
• těhotenství MeSH
• triglyceridy krev   MeSH
• zpožděný efekt prenatální expozice genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is increasing in parallel with obesity rates. Stress-related alterations in endoplasmic reticulum (ER), such as the unfolded protein response (UPR), are associated with obesity. The aim of this study was to investigate ER imbalance in the pancreas of a mice model of adult and perinatal diet-induced obesity. Twenty female C57BL/6J mice were assigned to control (Con) or obesogenic (Ob) diets prior to and during pregnancy and lactation. Their offspring were weaned onto Con or Ob diets up to 6 months post-partum. Then, after sacrifice, plasma biochemical analyses, gene expression, and protein concentrations were measured in pancreata. Offspring of Ob-fed mice had significantly increased body weight (p < 0.001) and plasma leptin (p < 0.001) and decreased insulin (p < 0.01) levels. Maternal obesogenic diet decreased the total and phosphorylated Eif2α and increased spliced X-box binding protein 1 (XBP1). Pancreatic gene expression of downstream regulators of UPR (EDEM, homocysteine-responsive endoplasmic reticulum-resident (HERP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP)) and autophagy-related proteins (LC3BI/LC3BII) were differently disrupted by obesogenic feeding in both mothers and offspring (from p < 0.1 to p < 0.001). Maternal obesity and Ob feeding in their offspring alter UPR in NAFPD, with involvement of proapoptotic and autophagy-related markers. Upstream and downstream regulators of PERK, IRE1α, and ATF6 pathways were affected differently following the obesogenic insults.

• MeSH
• autofagie MeSH
• biologické markery krev   metabolismus   MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• fyziologie výživy v mateřství * MeSH
• inzulin krev   MeSH
• komplikace těhotenství etiologie   patofyziologie   MeSH
• konzumní sacharóza škodlivé účinky   MeSH
• laktace MeSH
• leptin krev   MeSH
• myši inbrední C57BL MeSH
• obezita etiologie   patofyziologie   MeSH
• odstavení MeSH
• pankreas imunologie   metabolismus   patofyziologie   MeSH
• pankreatitida etiologie   imunologie   metabolismus   patofyziologie   MeSH
• signální dráha UPR * MeSH
• stres endoplazmatického retikula * MeSH
• těhotenství MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

We investigated the regulation of hepatic ER stress in healthy liver and adult or perinatally programmed diet-induced non-alcoholic fatty liver disease (NAFLD). Female mice were fed either obesogenic or control diet before mating, during pregnancy and lactation. Post-weaning, offspring from each maternal group were divided into either obesogenic or control diet. At six months, offspring were sacrificed at 4-h intervals over 24 h. Offspring fed obesogenic diets developed NAFLD phenotype, and the combination of maternal and offspring obesogenic diets exacerbated this phenotype. UPR signalling pathways (IREα, PERK, ATF6) and their downstream regulators showed different basal rhythmicity, which was modified in offspring exposed to obesogenic diet and maternal programming. The double obesogenic hit increased liver apoptosis measured by TUNEL staining, active caspase-3 and phospho-JNK and GRP78 promoter methylation levels. This study demonstrates that hepatic UPR is rhythmically activated. The combination of maternal obesity (MO) and obesogenic diets in offspring triggered altered UPR rhythmicity, DNA methylation and cellular apoptosis.

• MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• endoplazmatické retikulum fyziologie   MeSH
• fyziologický stres účinky léků   MeSH
• homeostáza MeSH
• játra účinky léků   MeSH
• krmivo pro zvířata analýza   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita chemicky indukované   metabolismus   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.

• MeSH
• bakteriální toxiny analýza   MeSH
• jezera mikrobiologie   MeSH
• klimatické změny MeSH
• látky znečišťující vodu analýza   MeSH
• mikrocystiny analýza   MeSH
• monitorování životního prostředí MeSH
• sinice * MeSH
• teplota MeSH
• tropany analýza   MeSH
• uracil analogy a deriváty   analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

• MeSH
• autofagie * fyziologie   MeSH
• biotest metody   normy   MeSH
• lidé MeSH
• počítačová simulace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• směrnice MeSH

• MeSH
• podpora zdraví MeSH
• primární prevence * MeSH
• zdravé chování MeSH
• životní styl MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• všeobecné lékařství

• MeSH
• lékařská informatika MeSH
• Publikační typ
• kongresy MeSH
• sborníky MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• lékařská informatika